Chih-Ming Liang

The Efficacy of Second‐Line Anti‐Helicobacter pylori Therapy Using an Extended 14‐Day Levofloxacin/Amoxicillin/Proton‐Pump Inhibitor Treatment – A Pilot Study

Large meta‐analyses of second‐line Helicobacter pylori eradication with fluoroquinolone triple therapy have shown that neither 7‐day nor 10‐day therapy provides 90% or better treatment success. Reports describing second‐line H. pylori eradication using 14‐day fluoroquinolone‐containing triple therapy are few. Current study aimed to determine the efficacy of a 14‐day levofloxacin/amoxicillin/proton‐pump inhibitor regimen as second‐line therapy and the clinical factors influencing the outcome.

The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication

Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests that tailored levofloxacin-containing therapy should be administered only for patients with susceptible strains because it can achieve >90% success rates.

Ten-Day versus 14-Day Levofloxacin-Containing Triple Therapy for Second-Line Anti-Helicobacter pylori Eradication in Taiwan.

Second-line Helicobacter pylori (H. pylori) eradication with fluoroquinolone-containing triple therapy is one of the recommended treatment options, but neither 7-day nor 10-day regimens provide >90% success rates. The current retrospective study aimed to clarify the effects of 10-day and 14-day levofloxacin-containing triple therapies for second-line H. pylori eradication in a Taiwanese cohort and to evaluate the potential clinical factors influencing eradication. A total of 200 patients who failed H. pylori eradication using the standard triple therapy were prescribed with either a 10-day (EAL-10) or a 14-day (EAL-14) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Follow-up studies to assess treatment response were carried out 8 weeks later. Eradication rates attained by EAL-10 and EAL-14 were 75.6%; 95% CI = 63.9–85.3% and 92.5%; 95% CI = 84.5–98.1%, P = 0.002 in the per protocol analysis and 68%; 95% CI = 56.6–78.5% and 86%; 95% CI = 76.8–93.4%, P = 0.002 in the intention-to-treat analysis. The duration of H. pylori therapy is the independent risk factor of H. pylori eradication (P = 0.003). In conclusion, 14-day levofloxacin-containing triple therapy can provide a >90% H. pylori eradication rate, but 10-day treatment duration may be suboptimal. The longer duration of H. pylori therapy (14 days) is the independent risk factor.

Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis

BackgroundMany studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs.MethodsSubjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27).ResultsAn initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group).ConclusionIntravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.

Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan

AIM To determine changes in the antibiotic resistance of Helicobacter pylori (H. pylori) in southern Taiwan after failure of first-line standard triple therapy. METHODS We analyzed 137 H. pylori-infected isolates from patients who experienced eradication failure after standard first-line triple therapy from January 2010 to December 2014. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the E-test method. The minimal inhibitory concentration (MIC) was determined by the agar dilution test. MIC values of ≥ 0.5, ≥ 1, ≥ 1, ≥ 4 and ≥ 8 mg/L were considered to be the resistance breakpoints for amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole, respectively. RESULTS A high resistance rate was found for clarithromycin (65%-75%) and metronidazole (30%-40%) among patients who failed first-line standard therapy. The resistance levels to amoxicillin and tetracycline remained very low; however, levofloxacin resistance was as high as 37.5% in 2010 but did not increase any further during the past 5 years. The rates of resistance to these antibiotics did not show a statistically significant upward or downward trend. CONCLUSION Antibiotic resistance of H. pylori remains a problem for the effective eradication of this pathogen and its associated diseases in Taiwan. High clarithromycin resistance indicated that this antibiotic should not be prescribed as a second-line H. pylori eradication therapy. Moreover, levofloxacin-based second-line therapy should be used cautiously, and the local resistance rates should be carefully monitored.

Levofloxacin-containing second-line anti-Helicobacter pylori eradication in Taiwanese real-world practice.

Background: Quinolone-containing triple therapy is recommended as an option for non-bismuth containing second-line Helicobacter pylori eradication. Current available Taiwanese reports in the literature used 7-day quinolone-containing triple therapy. As a result, some physicians still prescribe 7-day regimens in real-world practice in Taiwan. This study aimed to further assess the appropriateness of 7-day levofloxacin-containing triple therapy as second-line therapy. Methods: We enrolled 61 patients who failed H. pylori eradication using the standard triple therapy for 7 days and were prescribed levofloxacin-containing second-line triple therapy (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Routine follow-up with either endoscopy or urea breath test was done 8 weeks later to assess treatment response. Results: The eradication rates were 78.7% in the intention-to-treat analysis and 81% in the per-protocol analysis. The incidence of adverse events was 6.6%. Drug compliance was 95.1%. Antibiotic resistance showed the following results: Amoxicillin (0%), levofloxacin (23.5%), clarythromycin (35.3%), metronidazole (17.6%), and tetracycline (0%). Conclusion: The 7-day levofloxacin-containing triple therapy provides an unacceptable per-protocol report card as the second-line treatment for anti-H. pylori eradication in Taiwan and should be modified by either extending the duration to 10-14 days or seeking other regimens.

Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy.

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV‐1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non‐EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts ≥ 15 × 104/μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.

Impact factors for difficult cecal intubation during colonoscopy.

Background: There are no accepted means of identifying patients in whom colonoscopy is likely to be more difficult and allocate time accordingly. Aims: To identify patient-related, endoscopist-related, and procedure-related factors associated with difficult cecal intubation. Methods: This was a prospective study performed at the Kaohsiung Chang Gung Memorial Hospital, Kaohsiung Medical Center, from January to December 2009. Data pertaining to patient information (age, sex, weight, waist circumference and buttock girth, bowel habit, and abdomen surgery history) were recorded prospectively. Procedure-specific information including the need to alter patient position, application of external compression, and cecal intubation time (CIT) was documented. Results: A total of 859 consecutive patients were enrolled. The mean age of the patients was 50.5±11.4 years. CIT was longer in women compared with men (410±195 vs. 376±224 s; P=0.021). Older patients had longer CITs—an additional 2.1 seconds for each incremental year (P=0.001), and poor bowel preparation increased CIT (P=0.019). Patients who required a position change or abdominal compression took longer to reach the cecum (P<0.001). Conclusions: Our findings emphasize the importance of colon preparation and the need for abdominal compression and a change of position when performinga difficult colonoscopy.

Associated factors in Streptococcus bovis bacteremia and colorectal cancer.

Reports suggest that between 25% and 80% of patients with Streptococcus bovis/gallolyticus bacteremia have concomitant colorectal tumors. This retrospective study was aimed to identify associations between clinical characteristics and a finding of colorectal neoplasm in patients with S. bovis bacteremia who had colonoscopy examination. We retrospectively reviewed the records of patients with S. bovis bacteremia from Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, between January 2004 and January 2014. Clinical data including age, sex, comorbidities, blood culture, and colonoscopy findings were collected and their relationship to a finding of colorectal cancer was examined. A total of 107 patients with S. bovis bacteremia were identified, of whom 49 (72% male; age 65 ± 12 years) were investigated with colonoscopy; 15 of these patients (30.6%) had colorectal adenocarcinoma. Female sex (p = 0.014) and a history of noncolorectal malignancy (p = 0.004) were associated with a finding of colorectal adenocarcinoma. There were no associations with age, percentage of blood cultures, or the presence of diabetes mellitus, chronic liver disease, heart disease, or end‐stage renal disease. Our results show that S. bovis bacteremia is associated with the presence of colorectal adenocarcinoma, especially in female patients, and concomitant existence of other malignancies.

The Association of Helicobacter pylori Eradication with the Occurrences of Chronic Kidney Diseases in Patients with Peptic Ulcer Diseases

The association of Helicobacter pylori eradication with the occurrence of renal dysfunction in patients with peptic ulcer diseases is still unclear. This study aimed to clarify the relevance of H. pylori eradication to the occurrence of chronic kidney diseases in patients with peptic ulcer diseases. Data that were available from 2000–2011 were extracted from the National Health Insurance Research Database in Taiwan, and all patients with peptic ulcer diseases (n = 208 196) were screened for eligibility. We divided randomly selected patients into an H. pylori eradication cohort (cohort A, n = 3593) and matched them by age and sex to a without H. pylori eradication cohort (cohort B, n = 3593). Subgroup analysis was further performed for H. pylori eradication within ≤ 90 days of the diagnosis date (early eradication, n = 2837) and within 91–365 days (non-early eradication, n = 756). Cox proportional hazards regression analysis was used to estimate the association of H. pylori eradication with the risk of developing chronic kidney diseases and mortality. We observed that there were more patients suffering from chronic kidney disease in cohort B than in the early eradication subgroup of cohort A (8.49% vs. 6.70%, respectively, p = 0.0075); the mortality rate was also higher in cohort B (4.76% vs. 3.70%, respectively, p = 0.0376). Old age, pulmonary disease, connective tissue disorders, and diabetes were risk factors for chronic kidney diseases but early H. pylori eradication was a protective factor against chronic kidney diseases (hazard ratio: 0.68, 95% confidence interval: 0.52–0.88, p = 0.0030), and death (hazard ratio: 0.69, 95% confidence interval: 0.49–0.96, p = 0.0297). In conclusion, our findings have important implications suggesting that early H. pylori eradication is mandatory since it is associated with a protective role against the occurrence of chronic kidney diseases.